Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes
Background: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identificatio...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1298457/full |
| _version_ | 1797305119714312192 |
|---|---|
| author | Fang-Li Pei Jin-Jin Jia Shu-Hong Lin Xiao-Xin Chen Li-Zheng Wu Zeng-Xian Lin Bo-Wen Sun Cheng Zeng |
| author_facet | Fang-Li Pei Jin-Jin Jia Shu-Hong Lin Xiao-Xin Chen Li-Zheng Wu Zeng-Xian Lin Bo-Wen Sun Cheng Zeng |
| author_sort | Fang-Li Pei |
| collection | DOAJ |
| description | Background: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identification and clinical significance of efferocytosis-related genes (EFRGs) in EM is sparse.Methods: The EFRDEGs (differentially expressed efferocytosis-related genes) linked to datasets associated with endometriosis were thoroughly examined utilizing the Gene Expression Omnibus (GEO) and GeneCards databases. The construction of the protein-protein interaction (PPI) and transcription factor (TF) regulatory network of EFRDEGs ensued. Subsequently, machine learning techniques including Univariate logistic regression, LASSO, and SVM classification were applied to filter and pinpoint diagnostic biomarkers. To establish and assess the diagnostic model, ROC analysis, multivariate regression analysis, nomogram, and calibration curve were employed. The CIBERSORT algorithm and single-cell RNA sequencing (scRNA-seq) were employed to explore immune cell infiltration, while the Comparative Toxicogenomics Database (CTD) was utilized for the identification of potential therapeutic drugs for endometriosis. Finally, immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to quantify the expression levels of biomarkers in clinical samples of endometriosis.Results: Our findings revealed 13 EFRDEGs associated with EM, and the LASSO and SVM regression model identified six hub genes (ARG2, GAS6, C3, PROS1, CLU, and FGL2). Among these, ARG2, GAS6, and C3 were confirmed as diagnostic biomarkers through multivariate logistic regression analysis. The ROC curve analysis of GSE37837 (AUC = 0.627) and GSE6374 (AUC = 0.635), along with calibration and DCA curve assessments, demonstrated that the nomogram built on these three biomarkers exhibited a commendable predictive capacity for the disease. Notably, the ratio of nine immune cell types exhibited significant differences between eutopic and ectopic endometrial samples, with scRNA-seq highlighting M0 Macrophages, Fibroblasts, and CD8 Tex cells as the cell populations undergoing the most substantial changes in the three biomarkers. Additionally, our study predicted seven potential medications for EM. Finally, the expression levels of the three biomarkers in clinical samples were validated through RT-qPCR and IHC, consistently aligning with the results obtained from the public database.Conclusion: we identified three biomarkers and constructed a diagnostic model for EM in this study, these findings provide valuable insights for subsequent mechanistic research and clinical applications in the field of endometriosis. |
| first_indexed | 2024-03-08T00:21:17Z |
| format | Article |
| id | doaj.art-c15b2056c76a4a748bad0b54f04e0f51 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-08T00:21:17Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-c15b2056c76a4a748bad0b54f04e0f512024-02-16T09:36:12ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-01-011010.3389/fmolb.2023.12984571298457Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genesFang-Li Pei0Jin-Jin Jia1Shu-Hong Lin2Xiao-Xin Chen3Li-Zheng Wu4Zeng-Xian Lin5Bo-Wen Sun6Cheng Zeng7The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaBackground: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identification and clinical significance of efferocytosis-related genes (EFRGs) in EM is sparse.Methods: The EFRDEGs (differentially expressed efferocytosis-related genes) linked to datasets associated with endometriosis were thoroughly examined utilizing the Gene Expression Omnibus (GEO) and GeneCards databases. The construction of the protein-protein interaction (PPI) and transcription factor (TF) regulatory network of EFRDEGs ensued. Subsequently, machine learning techniques including Univariate logistic regression, LASSO, and SVM classification were applied to filter and pinpoint diagnostic biomarkers. To establish and assess the diagnostic model, ROC analysis, multivariate regression analysis, nomogram, and calibration curve were employed. The CIBERSORT algorithm and single-cell RNA sequencing (scRNA-seq) were employed to explore immune cell infiltration, while the Comparative Toxicogenomics Database (CTD) was utilized for the identification of potential therapeutic drugs for endometriosis. Finally, immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to quantify the expression levels of biomarkers in clinical samples of endometriosis.Results: Our findings revealed 13 EFRDEGs associated with EM, and the LASSO and SVM regression model identified six hub genes (ARG2, GAS6, C3, PROS1, CLU, and FGL2). Among these, ARG2, GAS6, and C3 were confirmed as diagnostic biomarkers through multivariate logistic regression analysis. The ROC curve analysis of GSE37837 (AUC = 0.627) and GSE6374 (AUC = 0.635), along with calibration and DCA curve assessments, demonstrated that the nomogram built on these three biomarkers exhibited a commendable predictive capacity for the disease. Notably, the ratio of nine immune cell types exhibited significant differences between eutopic and ectopic endometrial samples, with scRNA-seq highlighting M0 Macrophages, Fibroblasts, and CD8 Tex cells as the cell populations undergoing the most substantial changes in the three biomarkers. Additionally, our study predicted seven potential medications for EM. Finally, the expression levels of the three biomarkers in clinical samples were validated through RT-qPCR and IHC, consistently aligning with the results obtained from the public database.Conclusion: we identified three biomarkers and constructed a diagnostic model for EM in this study, these findings provide valuable insights for subsequent mechanistic research and clinical applications in the field of endometriosis.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1298457/fullendometriosisefferocytosisimmune infiltrationbioinformaticsand machine learning |
| spellingShingle | Fang-Li Pei Jin-Jin Jia Shu-Hong Lin Xiao-Xin Chen Li-Zheng Wu Zeng-Xian Lin Bo-Wen Sun Cheng Zeng Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes Frontiers in Molecular Biosciences endometriosis efferocytosis immune infiltration bioinformatics and machine learning |
| title | Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes |
| title_full | Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes |
| title_fullStr | Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes |
| title_full_unstemmed | Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes |
| title_short | Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes |
| title_sort | construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis related genes |
| topic | endometriosis efferocytosis immune infiltration bioinformatics and machine learning |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1298457/full |
| work_keys_str_mv | AT fanglipei constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT jinjinjia constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT shuhonglin constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT xiaoxinchen constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT lizhengwu constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT zengxianlin constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT bowensun constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes AT chengzeng constructionandevaluationofendometriosisdiagnosticpredictionmodelandimmuneinfiltrationbasedonefferocytosisrelatedgenes |